EP4687795A1

EP4687795A1 - Functionalised polymer material pad for treating skin cavity wounds

Info

Publication number: EP4687795A1
Application number: EP23793050.8A
Authority: EP
Inventors: Daniele PIETRA; Alice BORGHINI
Original assignee: Dealfa Srl
Current assignee: Dealfa Srl
Priority date: 2022-10-11
Filing date: 2023-10-10
Publication date: 2026-02-11
Also published as: WO2024079613A1; IT202200020859A1

Abstract

The present invention relates to a pad of poly(lactic-co- glycolic) acid-based polymer material, functionalised with dextran, maltodextrin, collagen, citric acid, chitosan, polyphenols, colloidal silver, hyaluronic acid and/or salts thereof, polyethylene glycol and alginate. The present invention further relates to a process for manufacturing the pad, and use of the pad in treating non-necrotic skin cavity wounds.

Description

FUNCTIONALISED POLYMER MATERIAL PAD FOR TREATING SKIN CAVITY

WOUNDS

DESCRIPTION

FIELD OF THE INVENTION

The present invention relates to an advanced dressing, the use thereof in treating non-necrotic skin cavity wounds, and a manufacturing process thereof.

BACKGROUND OF THE INVENTION

A product which promotes the tissue repair process, protecting the wound from infection and maintaining optimal moisture and oxygen permeability of the wound microenvironment is an advanced dressing.

Advanced dressings can be divided into:

PASSIVE - Used to absorb exudates and protect the lesion from external agents.

INTERACTIVE or ACTIVE - They play an active role in tissue repair by regulating the microenvironment of the lesion and ensuring the ideal characteristics for the repair process to be facilitated .

BIOACTIVE - They interact with reparative processes, releasing or forming substances which act directly on healing processes.

In the presence of certain skin lesions, the application of advanced dressings which promote healing can be useful. Lesions which may benefit from the application of advanced dressings are wounds, ulcers, and skin sores, such as diabetic ulcers, pressure ulcers and sores (bedsores), general skin ulcers and sores, surgical wounds, stab wounds, puncture wounds, gunshot wounds, burns.

In more detail, cavity wounds are deep lesions which exceed the dermo-epidermal plane and involve one or more of the following planes: subcutaneous, fascial, muscular and tendon. Usually, a cavity wound occurs as a result of surgical intervention (for example a surgical dehiscence, i.e., the spontaneous opening of a surgical wound after previous adhesion of the margins thereof, which may be caused by infection or maceration), trauma or a chronic ulcer (for example pressure ulcers, caused by ischaemia of the tissue planes as a result of prolonged pressure load).

In particular, pressure ulcers are areas of tissue damage to the skin and/or underlying tissues caused primarily by pressure, stretching or friction. Although largely preventable, this type of damage (also called pressure ulcer, sore, ulcer or bedsore) is a significant phenomenon in hospital wards and in the territory, both for the number of patients involved and for the time and resources needed to treat the problem.

Vascular lesions of the lower limbs are defined as those skin wounds of venous, arterial and/or mixed vascular aetiology, which are localized below the knee down to the foot and which last for at least eight to ten weeks. Chronic leg ulcers are a very frequent disease in the Western world, which mainly affects the elderly, resulting in a high social cost.

Diabetic ulcers, in particular those responsible for the diabetic foot, occur when diabetic neuropathy or lower limb arterial disease comprises the function or structure of the foot. The two cases, also defined as neuropathic foot or ischaemic foot, are profoundly different from each other: however, in most subjects, especially of advanced age, both coexist giving rise to the so-called neuroischaemic foot.

The surgical wound is a tissue continuity solution produced by a mechanical agent. In clinical practice, two main types of surgical wounds can be found:

- wounds which heal at the first attempt, in which the flaps have been brought together by applying a suture. They repair quickly, generally developing a linear scar which is often not very visible;

- wounds which heal at the second attempt, in which the flaps are not joined, often due to an infection. The healing is slow and the scar which forms can vary in size.

Stab wounds are one of the most common household accidents and are due to sharp objects such as knives or glass. They typically appear as linear, net-margin wounds.

Puncture wounds are due to sharp objects (daggers, nails, etc.) which cause lesions which are more developed at depth than on the surface. In addition to the entry hole, these wounds have a path which goes deep and can even take on the characteristics of penetrating or piercing wounds when the presence of an exit hole is also observed.

Gunshot wounds are produced by projectiles (bullets or splinters) of various shapes and sizes issued by weapons or produced by the explosion of explosive devices. When the bullet is animated by a very high penetration force, it can exit from the affected organism through an exit hole: this usually appears larger and more open than the entry hole because the bullet drags fragments of tissue therewith which increase the size thereof along its path.

A burn is an acute wound of traumatic origin caused by contact with a flame, with overheated liquids or solids, chemicals, electricity, or radiant energy. Depending on the depth thereof, they are divided into 1st and 2nd superficial degree, 2nd deep degree and 3rd degree burns; the optimal treatment of the first two is the dressing which generally allows healing within two weeks; in the case of deep burns, the best treatment is surgery.

Various substances or products show properties useful for the regeneration of tissues affected by wounds. Moreover, several attempts are known, from products on the market or from scientific and patent literature, to associate various substances in order to try to obtain effective dressings to promote the tissue repair process, protecting against infections and maintaining the optimal microenvironment.

Although several attempts are known (from commercially available products or from scientific and patent literature) to combine various substances to try to obtain effective dressings to promote the tissue repair process, protecting against infections and maintaining optimal conditions of moisture and oxygen permeability of the wound microenvironment, the need is still felt to be able to combine different substances with different properties, in such proportions as to exhibit synergistic effects in terms of promoting the tissue repair process, protecting against infections and maintaining optimal conditions of moisture and oxygen permeability of the wound microenvironment and at the same time able to be well tolerated and easy to apply.

In fact, there are various technical problems that an ideal advanced cavity dressing should solve. In particular, such dressings should:

- act as a vehicle for active ingredients,

- show very low toxicity/cytotoxicity towards the injured tissue in the healing phase, but be active against microorganisms, so as to ensure the control of the microbial load,

- be well tolerated, comfortable and not painful,

- be suitable for prolonged and repeated use as well,

- be easy to apply,

- not require frequent changes,

- not be adherent to the tissue of the lesion,

- be easily removable/detachable, or be resorbable,

- preserve the wound margins,

- control unpleasant odours which can come from the lesion,

- allow the gaseous exchange of oxygen, carbon dioxide and water vapour with the environment,

- be impermeable to incoming external microorganisms,

- prevent or treat infection,

- ensure mechanical protection (protect the injury from possible trauma) - possibly, allow the monitoring of the repair process without the need to remove the dressing,

- be compatible with other possible drugs or treatments to be applied to the wound bed (for example antimicrobial drugs, analgesics, anti-inflammatory drugs, local anaesthetics, and the like), with therapies such as negative pressure and with any secondary dressings used as a supplement or for fixing primary dressings.

Overall, therefore, they should have a good compliance by the subjects who are medicated therewith, for example by providing an effective dose of several active ingredients which act in synergy, and chemical-physical, mechanical and biocompatibility features such that frequent applications are not required, i.e., preferably they are applicable once a week or less frequently.

SUMMARY OF THE INVENTION

The above object has been achieved by an advanced dressing characterised by a poly (lactic-co-glycolic) acid-based polymer material pad, comprising: dextran maltodextrin collagen citric acid chitosan polyphenols colloidal silver hyaluronic acid and/or salts thereof polyethylene glycol alginate.

The advanced dressing of the invention is a primary, nonadherent, antiseptic, hydrophobic dressing to be positioned in the wound bed, which may be associated with a secondary dressing such as a non-woven gauze, a cotton gauze, and/or a fastening system such as a self-adhering bandage or patch, and the like.

The inventors of the present invention have surprisingly found that the above ingredients (dextran, maltodextrin, collagen, citric acid, chitosan, polyphenols, colloidal silver, hyaluronic acid and/or salts thereof, polyethylene glycol, alginate) when incorporated in a poly (lactic-co-glycolic) acid-based polymer material pad, show synergistic activity with each other in terms of low adhesiveness (rendering the dressing painless at the time of change/removal), antimicrobial power (protecting from exogenous infections), haemostatic power, stimulation of the tissue regeneration process, maintenance of optimal moisture conditions and oxygen permeability of the wound microenvironment.

Therefore, the present invention relates to an advanced dressing characterised by a pad of poly (lactic-co-glycolic) acidbased polymer material, functionalised with an active ingredient composition comprising or consisting of: dextran maltodextrin collagen citric acid chitosan polyphenols colloidal silver hyaluronic acid and/or salts thereof polyethylene glycol alginate, as outlined in the appended claims 1 to 8.

The invention also relates to a process for manufacturing the advanced dressing, as outlined in the appended claim 9.

The invention further relates to a composition comprising or consisting of: dextran maltodextrin collagen citric acid chitosan polyphenols colloidal silver hyaluronic acid and/or salts thereof polyethylene glycol alginate, for use in the treatment of non-necrotic skin cavity wounds, as outlined in the appended claims 10 and 11.

In fact, lesions which, in particular, can benefit from the application of the advanced dressing of the present invention are non-necrotic cavity wounds of the skin such as, but not limited to, diabetic ulcers, pressure ulcers and sores (bedsores), general skin ulcers and sores, surgical wounds, stab wounds, puncture wounds, gunshot wounds, burns and, in general, wounds in which the depth is such as to affect the subcutaneous, fascial, muscular and tendon planes.

The text of the appended claims forms an integral part of the present description for the purposes of evaluation of enabling disclosure.

Further features and advantages of the advanced dressing and process according to the invention will become apparent from the following description of embodiments thereof, given by way of non-limiting indication.

BRIEF DESCRIPTION OF THE DRAWINGS

Figures 1-3 show enlarged microscopic views of a functionalised polymer material pad, in which some pores and the dimensions thereof are highlighted.

Figure 4 shows a packaging example of the advanced dressing of the invention in a sterile vial.

DETAILED DESCRIPTION OF THE INVENTION

According to a first embodiment, the present invention relates to a pad of poly (lactic-co-glycolic) acid-based polymer material, functionalised with an active ingredient composition comprising or consisting of: dextran maltodextrin collagen citric acid chitosan polyphenols colloidal silver hyaluronic acid and/or salts thereof polyethylene glycol alginate.

According to certain embodiments of the invention, said active ingredient composition is characterised by the following percentages by weight, calculated on the total weight of the mixture of said components:

40 to 60% w/w dextran

12 to 25% w/w maltodextrin

5 to 10% w/w collagen

5 to 10% w/w citric acid

2 to 10% w/w chitosan

0.05 to 2.5% w/w polyphenols

0.001 to 0.005% w/w colloidal silver

1 to 8% w/w hyaluronic acid and/or salts thereof

1 to 5% w/w polyethylene glycol

1 to 5% w/w alginate.

According to a preferred embodiment of the invention, said active ingredient composition is characterised by the following percentages by weight, calculated on the total weight of the mixture of said components:

45 to 55% w/w dextran

15 to 20% w/w maltodextrin

6 to 9% w/w collagen

6 to 9% w/w citric acid

4 to 7% w/w chitosan

0.1 to 1% w/w polyphenols 0.001 to 0.005% w/w colloidal silver

2 to 5% w/w hyaluronic acid and/or salts thereof

2 to 4% w/w polyethylene glycol

2 to 4% w/w alginate.

As used herein, the term "advanced cavity dressing" means an advanced dressing suitable for the treatment of skin cavity wounds. Primary and secondary cavity dressings exist: the primary dressings are placed and act directly on the wound bed, while the secondary dressings are used as a supplement, or for fixing the primary dressings. Non-limiting examples of primary dressings are alginates, hydrocolloids, hydrofibres, and polyurethane foams. Non-limiting examples of secondary dressings are non-woven fabric gauzes, cotton gauzes, and fastening systems such as self-adhering patches or bandages.

As used herein, the term "active ingredient composition" means a composition of substances which bring a therapeutic effect to the advanced dressing, in which preferably at least two or more substances have a synergistic effect on each other.

As used herein, the term "comprising" means that the active ingredient composition described above may contain other active substances, as will be defined below, or non-active substances, i.e., substances which do not bring a therapeutic effect to the advanced dressing.

Preferably, the advanced cavity dressing is in the form of a pad of poly (lactic-co-glycolic) acid-based polymer material, functionalised with active ingredients capable of promoting the tissue repair process, maintaining optimal moisture and oxygen permeability conditions of the wound microenvironment, preventing external microorganisms from entering by virtue of antimicrobial activity, giving haemostatic properties, and stimulating the tissue regeneration process.

Moreover, the advanced cavity dressing has physical and mechanical properties such as to make it well tolerated, comfortable and non-painful, easy to apply and remove (being nonadherent to the affected tissue) or resorbable, not harmful to the wound margins.

As used herein, the term "poly (lactic-co-glycolic) acid", also known as PLGA, is a copolymer which is used in many therapeutic devices approved by the Food and Drug Administration (FDA), by virtue of the biodegradability and biocompatibility thereof. It is synthesized by ring-opening copolymerization of two different monomers, the cyclic dimers (1,4-dioxane-2,5- diones) of glycolic acid and lactic acid. During polymerization, adjacent glycolic or lactic acid monomer units are linked together in the PLGA by ester bonds, thus obtaining a linear aliphatic polyester as a product. PLGA degrades by hydrolysis of the ester bonds thereof in the presence of water, producing monomers of lactic acid and glycolic acid origin. Under physiological conditions, these monomers are by-products of various metabolic pathways, and there is no systemic toxicity associated with the use of PLGA for drug-delivery applications or in biomaterials. It is also possible to adjust the degradation time of the polymer by altering the ratio of the monomers used during the synthesis. This property makes it suitable and versatile in the production of biomedical devices, such as grafts, sutures, implants, prosthetic devices, surgical sealing film, micro and nanoparticles. In the advanced dressing of the present invention, the poly (lactic-co-glycolic) acid copolymer acts both as a carrier of active ingredients, regulating the release thereof to the wound site, and promoting the maintenance of optimal moisture conditions and oxygen permeability of the wound microenvironment. Moreover, the poly (lactic-co-glycolic) acid copolymer acts as a scaffold for tissue regeneration.

As used herein, the term "poly (lactic-co-glycolic) acid-based polymer material pad" means a block consisting of PLGA intended for use in padding cavity wounds, for the purpose of providing a primary dressing to the wounds themselves.

As used herein, the term "dextran" means a variety of branched glucose polymers of varying molecular weight. Dextran is characterised by a sequence of D-glucose molecules linked to each other by means of an alpha 1-6 glycosidic bond with short branches in the alpha 1-2, 1-3 and 1-4 positions. Dextran appears as a water-soluble white powder and is classified according to molecular weight. It is soluble in water and acts as a binder with the polymer.

As used herein, the term "maltodextrin" means a water-soluble complex carbohydrate. It is obtained through chemical hydrolysis processes mainly from the breakdown of starches from grains (corn, oats, wheat, rice) or tubers (potatoes, tapioca). Based on the degree of transformation of these starches, maltodextrins are created, consisting of glucose molecules arranged in polymer chains of variable length. Maltodextrin is typically composed of a variety of chains which can range from 3 to 17 glucose units.

As used herein, the term "collagen" means the body's most abundant protein, where it is concentrated primarily in the bones, tendons, cartilage, skin, membranes, and blood vessels. In particular, collagen is one of the main components of connective tissue. At the cutaneous level, collagen contributes to maintaining skin firmness, tone, and turgidity. It is present in the dermis where, together with elastic fibres and glycosaminoglycans, it gives rise to that three-dimensional structure which supports and sustains the skin, giving it strength and elasticity.

As used herein, the term "citric acid" means 2-hydroxy-l,2,3- propanetricarboxylic acid. It appears as a solid, colourless substance with a raw formula C₆H₈O₇, soluble in water over a wide pH range. It can be found in fruit, especially of the genus Citrus.

As used herein, the term "chitosan" means a linear polysaccharide composed of D-glucosamine and N-acetyl-D- glucosamine, linked via (β(1—4) bonds. Chitosan is usually obtained through the deacetylation of chitin, generally extracted from the exoskeleton of crustaceans (crabs, shrimps, etc.) with aqueous solution of sodium hydroxide, or it can be of vegetable or fungal origin, i.e., obtained through the deacetylation of chitin present in fungi, in which it forms the main component of the cell wall. The features distinguishing various types of chitosans and responsible for the different properties thereof are viscosity, degree of acetylation and molecular weight. Viscosity is measured in a 1% aqueous solution of acetic acid and expressed in centipoise (cP). Viscosity is measured on a Brookfield model NDJ- 1 rotational viscometer usable in a viscosity range from 10 to 100,000 cP. At room temperature, 3.0 g of test sample are taken, previously dried at constant weight at 105±2°C, before being placed in 300 ml of water with stirring. 3.0 g of glacial acetic acid are then added and stirring is continued for one hour until the sample is completely dissolved. The rotational viscometer is then used to determine the viscosity at 20±l°C. The degree of acetylation is determined using NMR spectroscopy and varies between 0% and 40% while the molecular weight range varies between 3800 and 20,000 Dalton.

As used herein, the term "polyphenols" means the total amount of polyphenolic structure compounds, expressed as caffeic acid equivalents and determined analytically by the Folin-Ciocalteu method [Ainsworth EA and Gillespie KM, Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent, Nature Protocols 2007;2:875-875]. Non-limiting examples of polyphenols are tannic acid, quercetin, apigenin, resveratrol, isoflavones, catechins. Non-limiting examples of polyphenol sources are plant extracts such as green tea extract, chestnut, acai fruit extract, red vine extract, pomegranate extract, olive leaf extract, etc.

As used herein, the term "colloidal silver" means a compound based on silver particles. It appears as flakes or granular powder which are bright grey-black-blue in colour, substantially odourless, insoluble in alcohol and ether, slightly soluble in water.

As used herein, the terms "hyaluronic acid" and "hyaluronic acid and/or salts thereof" mean a non-sulphurised glycosaminoglycan, without a protein core, with the unbranched polysaccharide chain produced by the condensation of thousands of disaccharide units formed in turn by residues of glucuronic acid and N-acetylglucosamine, linked to each other alternately by β1-4 and β1-3 glycosidic bonds, as well as by intramolecular hydrogen bonds, which stabilize the conformations thereof. At physiological pH, the carboxyl groups of the glucuronic units are ionized, giving the hyaluronate molecule high polarity and consequently high solubility in water. By virtue of this property, hyaluronate is capable of complexing with many water molecules, achieving a high degree of hydration. Hyaluronic acid is one of the key components of the connective tissues of man and other mammals. It gives skin the particular resistance and shape retention properties thereof. Hyaluronic acids of different molecular weight exist; the latter can vary from 2 to 1,500 kDa. Hyaluronic acids of different molecular weight show different and characteristic values of viscosity of the aqueous solutions containing it, as well as different degrees of penetration inside the skin. As used herein, the terms "hyaluronic acid" and "hyaluronic acid and/or salts thereof" mean hyaluronic acids with various molecular weights and/or salts thereof, such as, but not limited to, sodium hyaluronates, and/or mixtures of hyaluronic acids with various molecular weights and/or salts thereof. As used herein, the term "polyethylene glycol", also known as PEG, polyethylene oxide (PEO), or polyoxyethylene (POE), IUPAC name poly (oxy-1,2-ethanedyl), a-hydro-ω-hydroxyethane-1,2-diol, ethoxylate, means a polymer prepared by polymerization of ethylene oxide. In general, polyethylene glycol has average molecular weight values between 300 and 10,000,000 g/mol. The physical properties of polyethylene glycol (such as viscosity) vary according to the average length of the macromolecules, i.e., the average number n of repetitive units, while the chemical properties remain almost unchanged. At low n values, polyethylene glycol is liquid, while as n grows it acquires the appearance of a waxy solid with a relatively low melting point. The absence of toxicity of PEG allows the use thereof in the pharmaceutical field and in particular for parenteral, topical, ophthalmic, oral and rectal pharmaceutical formulations, for example as hydrophilic bases for ointments, as suspending or viscosifying agents in emulsions, in the preparation of vehicles for parenteral formulations, as plasticizers in the production of films for tablets.

As used herein, the term "polyethylene glycol" means polyethylene glycol with any molecular weight value and/or mixtures of different polyethylene glycols with different molecular weight values.

As used herein, the term "alginate" means a chemical compound consisting of an alginic acid salt. Alginic acid salts are, but are not limited to, sodium salts, calcium salts, and potassium salts. Alginate is extracted from the cell walls of algae and looks like a rubber. It has several uses, both in the food field

(as an emulsifying, thickening, gelling agent) and in the pharmaceutical field. Alginate quickly absorbs water, this property makes it useful in absorbing exudates which may be present in wounds.

The components of the present dressing are all known and individually available on the market.

In certain embodiments, the pad according to the invention comprises or consists of, in its entirety, 15 to 20% by weight of a substrate of poly (lactic-co-glycolic) acid and 80 to 85% by weight of the active ingredient composition.

Preferably, the active ingredient composition contains from 2 to 5% by weight of a mixture of high molecular weight and low molecular weight hyaluronic acid or sodium hyaluronate in a ratio of about 1:1.

Preferably, the polyethylene glycol is PEG 4000.

The advanced dressing of the invention can also comprise further ingredients and excipients such as, but not limited to, local anaesthetic active ingredients, analgesic and antiinflammatory active ingredients, antimicrobial active ingredients, growth factors, cytokines, hormones, vitamins, minerals, plant extracts and oils and the like.

Local anaesthetic active ingredients are compounds or substances of synthetic or natural origin with local anaesthetic activity. Non-limiting examples of synthetic local anaesthetic active ingredients are procaine, chloroprocaine, lidocaine, prilocaine, bupivacaine, ropivacaine, levobupivacaine and the like. Non-limiting examples of local anaesthetic active ingredients of natural origin are mint essential oil, myrrh essential oil, eucalyptus essential oil, and the like.

Analgesic and anti-inflammatory active ingredients are compounds or substances of synthetic or natural origin with analgesic and anti-inflammatory activity. Non-limiting examples of synthetic analgesic and anti-inflammatory active ingredients are steroidal (for example cortisone drugs and the like) and nonsteroidal (for example NSAIDs and the like). Non-limiting examples of analgesic and anti-inflammatory active ingredients of natural origin are those contained in birch extracts (Betula pendula), cloves (Syzygium aromaticum), spirea (Spirea ulmaria), willow (Salix alba), and the like.

Non-limiting examples of antimicrobial active ingredients are bacteriostatic, bactericidal, fungistatic, fungicidal, virustatic, virucidal, and similar drugs, of both synthetic and natural origin.

Non-limiting examples of vegetable oils are essential oils with antimicrobial activity, such as tea tree oil (Melaleuca spp .), or oils with anti-inflammatory activity, such as copaiba oleoresin (Copalfera spp).

There are no particular restrictions on the shape and size of the advanced dressing of the invention, which can take, for example, the shape of a solid, in particular a cube, a parallelepiped, a cylinder, a sphere, and the like, with the three spatial dimensions x, y, z in the range of 5 mm to 50 mm, and contains pores of 0.3 microns to 0.8 microns in diameter. EXAMPLES

Example 1 - Poly (lactic-co-glycolic) acid-based pad

An advanced dressing in the form of a functionalised polymer material pad was prepared using the following ingredients (Table 1):

Table 1.

The aforesaid advanced dressing is produced by mixing the raw materials in the amounts indicated in Table 1, placing the mixture in dies of the desired shape and size, and subjecting the mixture in the dies to freeze-drying.

Example 2 - Evaluation of the kinetics of killing microorganisms inoculated on the advanced dressing

The purpose of the test is to establish whether the product in the conditions of use thereof shows efficacy in killing microbial flora. The activity is evaluated by contaminating the samples with a defined inoculum of selected strains of microorganisms and evaluating the killing of the contamination. The inoculation is performed with multiple microbial strains, Gram positive, Gram negative, yeasts, and moulds. At different but very close times, the residual microbial load for each strain is evaluated, up to 48 hours after inoculation. The inoculation was performed with five microbial strains at different concentrations, as shown in Table 2 below:

Table 2.

The concentration of viable cells was determined by the plate count method. The diluent which is used is a sodium chloride- peptone solution at pH 7 with the addition of some preservative neutralizing agents (polysorbate 80, soy lecithin, L-Histidine). The count of the microorganisms at the different times was performed by withdrawing 1 g of product and diluting it up to lxlO⁶ times. Each dilution was then plated in Petri dishes containing the agarised selective culture medium. The plates were incubated in a thermostat at 34±1°C (bacteria) or at 22±1°C (yeasts and moulds) for the time necessary to allow sufficient microorganism growth for counting purposes (18-24 h for bacteria, 3-7 days for yeasts and moulds). By correcting the number of colonies observed for the dilution factor, the CFU (Colony Forming Units) value is obtained per gram of product.

In addition to zero-time sowing, sowing is performed at later times so as to evaluate the regression curve of microbial killing (for bacteria after 10', 2 h, 4 h; for yeasts and moulds after 30', 4 h, 8 h, 24 h and 48 h).

The results are summarized in Tables 3-6 below.

Table 3. Total microbial counts at different analysis times.

Table 4. Log reduction of the microbial count.

Example 3 - Evaluation of the release of polyphenols from an advanced dressing in the form of a functionalised polymer material pad

The present study aimed to evaluate the release of polyphenols over time from an advanced dressing in the form of a functionalised polymer material pad.

A dressing weighing 1.5 g was placed in a crystallizer and wet with 20 ml of water. At the times shown below, a sample of 50 microlitres was taken from the aqueous solution in contact with the dressing, and the content of total polyphenols released over time was evaluated on this sample. Such an evaluation was done by Folin-Ciocalteau assay. The times were as follows: 10 minutes, 30 minutes, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours.

For the execution of the assay, the samples were placed in transparent microplate wells. In line A, a gallic acid solution was placed as a positive control, with 1:1 serial dilutions going from well Al to well A6. In lines B to H, the samples taken at the different times were placed, also subjected to 1:1 serial dilutions going from well 1 to well 6. For the gallic acid concentrations (expressed in mg/ml), see Table 5 below.

Table 5.

The results are summarized in Table 6 below, in which the estimated total polyphenol concentrations (x) released from the advanced dressing at the various times are expressed as mg/ml gallic acid.

Table 6. Example 4 - Application of the advanced dressing to a wound

Below is an exemplary procedure for applying the dressing.

1) Prepare the wound following a standard protocol or according to the doctor's instructions.

2) Clean the wound by irrigation with a sterile saline solution. If required, remove the foreign material, cellular debris and devitalized tissue from the lesion using suitable tools, or with the aid of the mechanical action of a jet of sterile saline solution.

3) Thoroughly dry the intact skin surrounding the wound, without touching the injured skin. If necessary, shave the hair around the wound.

4) Choose an amount of advanced dressing adapted to fill the wound cavity.

5) Gently introduce the suitably cut dressing into the wound cavity, so as to fill the spaces (padding), but without exerting pressure.

6) Then, apply a secondary covering dressing on the cavity wound, with the precaution of allowing the back to be inspectable so as to ascertain the degree of saturation of the exudate, and thereby establish the time of changing the primary dressing and the secondary dressing.

Claims

1. A pad made of poly (lactic-co-glycolic) acid functionalised with an active ingredient composition comprising or consisting of: dextran maltodextrin collagen citric acid chitosan polyphenols colloidal silver hyaluronic acid and/or salts thereof polyethylene glycol alginate.

2. The pad according to claim 1, wherein the active ingredient composition is characterised by the following weight percentages, based on the total weight of the dressing:

40 to 60% w/w dextran

12 to 25% w/w maltodextrin

5 to 10% w/w collagen

5 to 10% w/w citric acid

2 to 10% w/w chitosan

0.05 to 2.5% w/w polyphenols

0.001 to 0.005% w/w colloidal silver

1 to 8% w/w hyaluronic acid and/or salts thereof

1 to 5% w/w polyethylene glycol

1 to 5% w/w alginate.

3. The pad according to claim 1, wherein the active ingredient composition is characterised by the following weight percentages, based on the total weight of the dressing:

45 to 55% w/w dextran

15 to 20% w/w maltodextrin

6 to 9% w/w collagen

6 to 9% w/w citric acid

4 to 7% w/w chitosan

0.1 to 1% w/w polyphenols

0.001 to 0.005% w/w colloidal silver

2 to 5% w/w hyaluronic acid and/or salts thereof

2 to 4% w/w polyethylene glycol

2 to 4% w/w alginate.

4. The pad according to any one of claims 1 to 3, wherein the polyphenols are tannic acid.

5. The pad according to any one of claims 1 to 4, wherein the polyethylene glycol is polyethylene glycol 4000 (PEG4000), and/or the hyaluronic acid and/or salts thereof is an approximately 1:1 mixture of low molecular weight and high molecular weight hyaluronic acid and/or sodium hyaluronate.

6. The pad according to any one of claims 1 to 5, wherein the pad is in the shape of a solid, in particular a cube, a parallelepiped, a cylinder, a sphere, and the like, with the three spatial dimensions x, y, z in the range of 5 mm to 50 mm, and contains pores of 0.3 microns to 0.8 microns in diameter.

7. The pad according to any one of claims 1 to 6 further comprising additional active ingredients selected from the group consisting of: local anaesthetics, analgesics and antiinflammatory agents, antimicrobial agents, growth factors, cytokines, hormones, vitamins, minerals, plant extracts and oils, and the like.

8. The pad according to any one of claims 1 to 7 comprising or consisting of, in its entirety, 15 to 20% by weight of a substrate of poly (lactic-co-glycolic) acid and 80 to 85% by weight of the active ingredient composition.

9. A process for manufacturing a pad according to any one of claims 1 to 8, said process comprising the following steps:

- preparing the mixture containing the copolymer and the other active ingredients and excipients

- placing the mixture in dies with the desired shape and size

- freeze-drying the mixture in the dies

- sterilizing and packaging.

10. A composition comprising or consisting of:

40 to 60% w/w, or 45 to 55% w/w, dextran

12 to 25% w/w, or 15 to 20% w/w, maltodextrin

5 to 10% w/w, or 6 to 9% w/w, collagen

5 to 10% w/w, or 6 to 9% w/w, citric acid

2 to 10% w/w, or 4 to 7% w/w, chitosan

0,05 to 2,5% w/w, or 0,1 to 1% w/w, polyphenols

0.001 to 0.005% w/w, or 0.001 to 0.005% w/w, colloidal silver

1 to 8% w/w, or 2 to 5% w/w, hyaluronic acids and/or salts thereof

1 to 5% w/w, or 2 to 4% w/w, polyethylene glycols

1 to 5% w/w, or 2 to 4% w/w, alginate, for use in the treatment of non-necrotic skin cavity wounds.

11. The composition for use according to claim 10, wherein the non-necrotic skin cavity wounds are selected from the group consisting of: diabetic ulcers, pressure ulcers and sores (bedsores), general skin ulcers and sores, surgical wounds, stab wounds, puncture wounds, gunshot wounds, burns.